An In Vitro Robotic Assay for Anti-Estrogenic Activity

抗雌激素活性的体外机器人测定

• 批准号: 7494997
• 负责人: Cathy Z Yang
• 金额: $ 53.39万
• 依托单位: CERTICHEM, INC.
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-09-10 至 2010-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7494997
• 关键词: Adverse effects; Animal Feed; Antioxidants; Behavioral; Biological Assay; Cell Proliferation; Chemicals; Cosmetics; Data; Development; Diet; Endocrine; Endocrine Disruptors; Environment; Estrogens; Evaluation; Feasibility Studies; Food; Food Additives; Food Preservatives; Funding; Genes; Goals; Grant; Health; High Pressure Liquid Chromatography; Hormones; Human; In Vitro; Investigation; Knowledge; MCF7 cell; Mammals; Measures; Methods; Mission; National Toxicology Program; Numbers; One-Step dentin bonding system; Paper; Pesticides; Pharmacologic Substance; Phase; Physiological Processes; Plastics; Polymers; Prevalence; Reporting; Reproducibility; Robotics; Sampling; Scientist; Screening procedure; Silicones; Small Business Funding Mechanisms; Small Business Innovation Research Grant; Testing; Time; Transcriptional Activation; United States Environmental Protection Agency; United States Food and Drug Administration; United States National Institutes of Health; Validation; Work; Writing; chemical release; commercial application; commercialization; consumer product; cost effective; design; desire; estrogenic activity; experience; fetal; in vivo; monomer; reproductive; social

DESCRIPTION (provided by applicant): Recent scientific investigations have shown that many chemicals used in plastics, pharmaceuticals, pesticides, cosmetics, food additives, etc., are endocrine disruptors (EDs). EDs interfere in various ways with hormones such as estrogens to have significant adverse effects on many behavioral and physiological processes. ED effects (e.g. estrogenic or anti-estrogenic) sometimes occur at very low (picomolar to nanomolar) concentrations, especially on fetal or developing mammals (including humans). The prevalence and actions of EDs in our environment warrant the development of valid assay methods. Consequently, various governmental bodies (e.g., EPA, FDA, and ICCVAM) and proactive corporations have explicitly expressed a desire to have in vitro robotic assays for EDs, such as anti-estrogenic activity (anti-EA). However, no robotic anti-EA assay is commercially available. To begin to meet these governmental, scientific and commercial needs, CertiChem (CCi) has completed a Phase I SBIR grant showing that it is feasible to develop an anti- EA robotic assay that would be valid (i.e., reliable, accurate, versatile, rapid, and cost effective) using MCF-7 cells. In this Phase II application, CCi now proposes to develop this robotic assay for anti-EA for commercialization by repeatedly assaying a set of 78 reference test chemicals to confirm the reliability and accuracy of CCi's proposed anti- EA assay. CCi also proposes to demonstrate the versatility of this assay by examining the anti-EA in a set of antioxidants used in foodstuffs and plastics. Finally, CCi proposes to perform HPLC separation assays on some reference test chemicals to confirm that their anti-EA is not due to contamination and to enhance the versatility of this assay for commercial use. Development of a robotic screening assay for anti-EA is commercially, scientifically, and socially important because of the large number of chemicals (>10,000) - much less chemical mixtures - that should now be screened for anti-EA by profit, non-profit, or governmental entities. Development of a robotic assay for anti-EA is desired as part of the mission of NIEHS, EPA and ICCVAM. Recent scientific investigations have shown that many (perhaps over 10,000) chemicals used in common products such as plastics, pesticides, cosmetics, and food additives have estrogenic/anti-estrogenic activities that severely interfere with normal estrogen actions to produce adverse effects on many behavioral, reproductive, and physiological processes in humans. In this Phase II proposal, CertiChem (CCi) proposes to develop a very sensitive and accurate assay to measure anti-estrogenic activity in a set of reference test chemicals and in common consumer products. CCi proposes to use these data and CCi's data on estrogenic activity on many chemicals to identify which chemicals have anti-estrogenic activity and to work with various firms to design consumer products that are free of chemicals that release anti-estrogenic or estrogenic activities.

描述（由申请人提供）：最近的科学研究表明，塑料，药物，农药，化妆品，食品添加剂等中使用的许多化学物质都是内分泌干扰物（EDS）。 EDS通过各种方式干扰雌激素，例如雌激素对许多行为和生理过程产生重大不利影响。 ED效应（例如，雌激素或抗雌激素）有时会出现在非常低的（皮摩尔至纳米尔）浓度下，尤其是在胎儿或发育中的哺乳动物（包括人）上。 ED在我们环境中的流行和行动需要开发有效的测定方法。因此，各种政府机构（例如EPA，FDA和ICCVAM）和积极主动的公司明确表示希望对EDS进行体外机器人测定，例如抗雌激素活性（Anti-EA）。但是，没有机器人的防抗EA分析可获得。为了开始满足这些政府，科学和商业需求，Certichem（CCI）已完成了I期SBIR赠款，表明使用MCF-7细胞开发有效的反EA机器人测定法是有效的（即可靠，准确，通用，快速，快速和成本效益）的）。在此II阶段应用中，CCI现在建议通过反复测定一组78种参考测试化学品来确认CCI提出的抗EA测定法的可靠性和准确性，从而开发这种机器人分析，以进行抗应电子用于商业化。 CCI还建议通过在食品和塑料中使用的一组抗氧化剂中检查抗A，以证明该测定法的多功能性。最后，CCI建议在某些参考测试化学品上进行HPLC分离测定法，以确认其抗EA并非造成污染，并增强该测定的多功能性供商业用途。由于大量的化学物质（> 10,000）（> 10,000）（少得多的化学混合物），对反电子的机器人筛查测定法在商业上，科学和社会上很重要，现在应该通过利润，非营利组织或政府实体来筛选反电子产品。作为NIEHS，EPA和ICCVAM任务的一部分，需要开发针对反电子的机器人测定法。最近的科学研究表明，许多用于塑料，农药，化妆品和食物添加剂等常见产品中使用的化学物质（可能超过10,000种）具有雌激素/抗雌激素活性，这些活性严重干扰了正常的雌激素作用，以对许多行为，生殖，生殖和物理学过程产生不良影响。在此II阶段提案中，认证（CCI）提议开发一种非常敏感和准确的测定法，以测量一组参考测试化学物质和常见的消费产品中的抗源性活性。 CCI建议使用这些数据和CCI对许多化学物质的雌激素活性的数据，以确定哪些化学物质具有抗雌激素活性，并与各种公司一起设计，这些化学物质不含释放抗生殖或雌激素活性的化学物质。